SirT1: A Guardian at the Gates of Adipose Tissue Inflammation

Abstract

Chronic, low-grade inflammation in adipose tissue is a characteristic of obesity that is intrinsically connected with fat expansion. The induction and maintenance of adipose tissue inflammation limits the ability of adipocytes to properly store nutrients and is strongly associated with systemic and adipocyte insulin resistance. The identification of inflammation as a link between obesity and type 2 diabetes has led to an explosion in research addressing how inflammatory cells (e.g., adipose tissue macrophages [ATMs] and T lymphocytes) and proinflammatory signaling networks interact with nutrient excess. This research has identified critical pathways that accelerate (e.g., nuclear factor-κB [NF-κB] and c-Jun N -terminal kinase [JNK] [1]) as well as those that suppress inflammation (e.g., the n-3 fatty acid receptor GPR120 [2]). Modulation of these signals may hold the key to unlocking future treatments for diabetes and metabolic syndrome. The advances in the field of obesity-induced inflammation have shed new light on the dual ability of components of the innate immune system to control inflammation and nutrient metabolism (e.g., Toll-like receptors and the inflammasome). In line with this, Gillum et al. (3) present evidence that sirtuin 1 (SirT1) can function as a suppressor of adipose tissue inflammation. Their data lend further support to the concept that SirT1 sits at the nexus between energy homeostasis and inflammation. The sirtuins are a family of deacetylases that regulate nutrient use via their ability to modify gene expression and target histones, metabolic transcription factors, and coregulators (e.g., peroxisome proliferator–activated receptor γ [PPARγ] [4]). Their ability …